A single neuron is composed of several different cellular regions or domains -- soma, dendrites, axon, axon terminals -- each specialized to perform particular functions. These domains differ in their structure, in the constituents of their cell membranes, and in their interactions with other cells. We propose to study the development of individual hippocampal neurons in dispersed cell culture in order to understand how these aspects of cellular organization arise and how they are maintained. We shall examine the structural organization of isolated neurons in low-density cultures, using light, scanning, and transmission electron microscopy, in order to determine which of the characteristic features of dendrites and axons can develop in the absence of contacts with other cells. We shall also determine whether, under such conditions, membrane constituents become restricted to appropriate regions of the cell as they do in vivo. The distribution of receptors for acetylcholine and GABA and of voltage-sensitive sodium channels will be assessed using specific, high-affinity ligands (Alpha-bungaro-toxin and quinuclidinyl benzilate, muscimol, and scorpion toxin). Radioactive derivatives of these compounds will be visualized by light microscopic autoradiography, and in addition, ferritin conjugates of Alpha-bungarotoxin will be prepared and visualized by scanning electron microscopy. In higher-density cultures which permit extensive cellular contacts, we shall study the types of synapses present and their localization over the cell surface, correlating this with the regional domains identified on the basis of internal and cell-surface features. Finally we shall study the stages of neuronal development in culture in order to determine when these aspects of regional organization become apparent.